Fig. 6: KIRREL1 restricts YAP/TAZ activity during ductular reaction (DR) in mice.

a Kirrel1 ISH co-staining with the BEC marker CK19 in Kirrel1:AlbCre and WT control mice. PV portal vein. Arrowheads indicate Kirrel1 ISH signals in periportal hepatocytes. Scale bar, 50 µm. b Scheme depicting 16 days DDC diet injury in Kirrel1:AlbCre and control mice. c Kirrel1 ISH co-staining with CK19 in control mice 16 days post DDC diet. PV, portal vein. Arrowheads indicate Kirrel1 ISH signals in encircled hepatocytes. Scale bar, 100 µm. d ISH for the YAP target gene Ctgf co-stained with CK19 and the hepatocyte marker Albumin (Alb), showing increased YAP signaling during DDC-induced DR in Kirrel1:AlbCre mice. PV, portal vein. Scale bar, 100 µm. e–g Co-staining for CK19, ALB, and SOX9 (e) in the indicated mice (arrowheads mark SOX9 + hepatocytes). Quantification indicates increased numbers of SOX9 + hepatocytes (f) and the percentage of CK19 staining per area (g, normalized to number of portal veins in the analysis area) in Kirrel1:AlbCre compared to control mice following 16 days DDC diet (IHC stainings used for quantification are provided in Fig. S6e). Data represent mean ± SD. Two-tailed unpaired t-test was used with groups of n = 4 control and n = 5 Kirrel1:AlbCre mice (6f, g). p values are 0.0090 (**, f), 0.0125 (*, g). Scale bar (e), 100 µm. h, i Co-staining for Ki67, CK19, and ALB (h) and quantification (i) indicates increased number of proliferating Ki67 + CK19 + BECs (arrowheads) in Kirrel1:AlbCre compared to control mice. PV portal vein, Data represent mean ± SD. Two-tailed unpaired t-test was used with groups of n = 4 control and n = 5 Kirrel1:AlbCre mice. p value is 0.00009 (****, i). Scale bar, 100 µm (h).